小鼠胚泡移植法在研究羟基脲发育毒性中的应用  

Application the mice blastocyst transplant technology to detect the hydroxyurea development toxicity

作　　者：王晓军[1] 王静[1] 管彤[1] 姜文玲[1] 杨友润[1] 

机构地区：[1]天津市卫生防病中心,天津300011

出　　处：《毒理学杂志》2006年第3期156-158,共3页Journal of Toxicology

摘　　要：目的探讨体外染毒后胚泡移植方法评价羟基脲发育毒性的可行性。方法由C57BL/6J雌性小鼠和DBA雄性小鼠交配产生BDF1小鼠,以BDF1雌性小鼠作为供胚鼠进行超排卵,并与BDF1雄性小鼠交配后采集受精卵,再以20μg/ml的羟基脲对着床前胚胎进行体外染毒,将染毒后可胚泡化的胚胎移植于假孕昆明种代母鼠体内继续生长发育,观察出生前胎鼠形态学改变和出生后子鼠的行为改变,并对子鼠大脑进行病理检查。结果(1)在实验剂量下,羟基脲染毒组胎鼠出生前形态学检查未见异常。(2)羟基脲染毒组子鼠出现行为异常:回旋运动、阴性趋地运动、翻正反射和断崖回避阳性日均迟于阴性对照组(P<0.05,P<0.01,P<0.05,P<0.05);悬挂时间短于阴性对照组(P<0.05);10日龄游泳积分低于阴性对照组(P<0.01)。(3)电镜超微结构显示染毒组子鼠大脑中毒性损伤。结论将胚胎体外培养和胚泡移植技术结合起来,排除母体因素的影响探究羟基脲的发育毒性,是一可行的方法。Objective To explore the method of embryos transplant technology in evaluating the development toxicity of hydroxyurea. Method First, C57BL/6J female mice mated with DBA male mice, to get their filial generation. Then, the female hybrid BDF1 ,selected as embryo-provider, superovulation and mated with male hybrids, to collect their fertilized ovums. The preimplantation blastocyst were exposed to hydroxyurea in vitro by 20 μg/ml hydroxyurea. After exposure, the treated blastocysts were transferred to the Kunming pseudopregnant surrogate mothers. The morphologic changes of the embryos before birth and the behavioral changes of offspring after birth were determined. The histopathology of the cerebrunl of offspring was also observed with electron microscope. Results （ 1 ） There were no gross dysmorphogenic effects in the exposed embryos. （2）The exposed offspring showed behavior abnormalities： circumnutation, negative ground tendency, surface righting reflex, delayed cliff avoidance positive days were all more late than control group.The time of suspending was shorter and the mark of 10-day swimming was lower compared with control group. （3）The examination of ultrastructure of electron microscope showed poisonous damage in the exposed offspring cerebrum. Conclusion The blastcyst transplant technology combined with blastocyst in vitro culture is a feasible way to detect the hydroxyurea development toxicity, and in this way the maternal effect can be avoided.

关 键 词：小鼠胚泡 羟基脲 体外染毒 胚泡移植 发育毒性 

分 类 号：R99[医药卫生—毒理学]